Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament–Derived Cells
Background: Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time af...
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| Veröffentlicht in: | The American journal of sports medicine 2017-05, Vol.45 (6), p.1359-1369 |
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| creator | Inokuchi, Takao Matsumoto, Tomoyuki Takayama, Koji Nakano, Naoki Zhang, Shurong Araki, Daisuke Matsushita, Takehiko Kuroda, Ryosuke |
| description | Background:
Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time after injury on the healing process is unclear.
Hypothesis:
Cells obtained during the early phase after injury will exhibit a greater tendon-bone healing potential compared with chronic phase counterparts when applied to an immunodeficient rat model of ACL reconstruction.
Study Design:
Controlled laboratory study.
Methods:
Adult human ACL-ruptured tissue was harvested from patients undergoing arthroscopic primary ACL reconstruction and classified into 2 groups based on the time elapsed between injury and surgery: (1) early group (≤3 months from injury) and (2) chronic group (>3 months from injury). In addition, 76 ten-week-old female immunodeficient rats underwent ACL reconstruction, followed by intracapsular administration of one of the following: (1) ACL-derived cells from the early group (n = 5), (2) ACL-derived cells from the chronic group (n = 5), or (3) phosphate-buffered saline (PBS) only (n = 5). During the 8 weeks after surgery, histological (weeks 2, 4, 8), immunohistochemical (week 2), radiographic (weeks 0, 2, 4, 8), and biomechanical (week 8) analyses were performed to evaluate tendon-bone healing.
Results:
In the early group, the histological evaluation showed early healing, induction of endochondral ossification–like integration, and mature bone ingrowth. Micro–computed tomography showed that the tibial bone tunnels at week 4 and week 8 were significantly reduced in the early group compared with those in the chronic group and PBS group (P < .05). Moreover, biomechanical tensile strength was significantly greater in the early group than in the other groups (P < .05). An accelerated healing potential in the early group was further demonstrated by the enhancement of intrinsic angiogenesis/osteogenesis and human-derived vasculogenesis/osteogenesis.
Conclusion:
Compared with human ACL-derived cells obtained during the chronic phase, cells obtained during the early phase after injury have a greater tendon-bone healing potential when used in an immunodeficient rat model of ACL reconstruction.
Clinical Relevance:
During ACL reconstruction surgery, transplanting ACL remnant tissue in the early phase after injury could accelerate and enhance tendon-bone heali |
| doi_str_mv | 10.1177/0363546517689871 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1876500822</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0363546517689871</sage_id><sourcerecordid>1898546896</sourcerecordid><originalsourceid>FETCH-LOGICAL-c431t-aba0e666ba2fa5abcffc9da16e7bbd59875bc7ce6442e367161348e6ddfe910a3</originalsourceid><addsrcrecordid>eNp1kc1KxDAUhYMoOv7sXUnAjZtq0jZpu5TxZwYGFNR1SdObsUObaNIMzs538A19ElNHRQTJIpDz3XNv7kHokJJTSrPsjCQ8YSlnNON5kWd0A40oY3GUJJxtotEgR4O-g3adWxBCBnAb7cR5OHEaj9DLVKvWg5aAjcL9I-CpXni7inoT3Xk7B7sKLz3YpWix0Z_EBETb6Dm-NT3ovhkEhSe-ExqfD2hjLB5bLxvRA541c9EF7P317SJIS6jxGNrW7aMtJVoHB1_3Hnq4urwfT6LZzfV0fD6LZJrQPhKVIMA5r0SsBBOVVEoWtaAcsqqqWfg0q2QmgadpDAnPKKdJmgOvawUFJSLZQydr3ydrnj24vuwaJ8MEQoPxrqR5xhkhYR0BPf6DLoy3OkwXqCIPi8wLHiiypqQ1zllQ5ZNtOmFXJSXlkEr5N5VQcvRl7KsO6p-C7xgCEK0BJ-bwq-t_hh-y95Zn</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1898546896</pqid></control><display><type>article</type><title>Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament–Derived Cells</title><source>MEDLINE</source><source>SAGE Publications</source><source>Alma/SFX Local Collection</source><creator>Inokuchi, Takao ; Matsumoto, Tomoyuki ; Takayama, Koji ; Nakano, Naoki ; Zhang, Shurong ; Araki, Daisuke ; Matsushita, Takehiko ; Kuroda, Ryosuke</creator><creatorcontrib>Inokuchi, Takao ; Matsumoto, Tomoyuki ; Takayama, Koji ; Nakano, Naoki ; Zhang, Shurong ; Araki, Daisuke ; Matsushita, Takehiko ; Kuroda, Ryosuke</creatorcontrib><description>Background:
Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time after injury on the healing process is unclear.
Hypothesis:
Cells obtained during the early phase after injury will exhibit a greater tendon-bone healing potential compared with chronic phase counterparts when applied to an immunodeficient rat model of ACL reconstruction.
Study Design:
Controlled laboratory study.
Methods:
Adult human ACL-ruptured tissue was harvested from patients undergoing arthroscopic primary ACL reconstruction and classified into 2 groups based on the time elapsed between injury and surgery: (1) early group (≤3 months from injury) and (2) chronic group (>3 months from injury). In addition, 76 ten-week-old female immunodeficient rats underwent ACL reconstruction, followed by intracapsular administration of one of the following: (1) ACL-derived cells from the early group (n = 5), (2) ACL-derived cells from the chronic group (n = 5), or (3) phosphate-buffered saline (PBS) only (n = 5). During the 8 weeks after surgery, histological (weeks 2, 4, 8), immunohistochemical (week 2), radiographic (weeks 0, 2, 4, 8), and biomechanical (week 8) analyses were performed to evaluate tendon-bone healing.
Results:
In the early group, the histological evaluation showed early healing, induction of endochondral ossification–like integration, and mature bone ingrowth. Micro–computed tomography showed that the tibial bone tunnels at week 4 and week 8 were significantly reduced in the early group compared with those in the chronic group and PBS group (P < .05). Moreover, biomechanical tensile strength was significantly greater in the early group than in the other groups (P < .05). An accelerated healing potential in the early group was further demonstrated by the enhancement of intrinsic angiogenesis/osteogenesis and human-derived vasculogenesis/osteogenesis.
Conclusion:
Compared with human ACL-derived cells obtained during the chronic phase, cells obtained during the early phase after injury have a greater tendon-bone healing potential when used in an immunodeficient rat model of ACL reconstruction.
Clinical Relevance:
During ACL reconstruction surgery, transplanting ACL remnant tissue in the early phase after injury could accelerate and enhance tendon-bone healing.</description><identifier>ISSN: 0363-5465</identifier><identifier>EISSN: 1552-3365</identifier><identifier>DOI: 10.1177/0363546517689871</identifier><identifier>PMID: 28282242</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Adult ; Animals ; Anterior Cruciate Ligament - cytology ; Anterior Cruciate Ligament - surgery ; Anterior Cruciate Ligament Reconstruction - methods ; Biomechanics ; Cell Differentiation ; Cell Proliferation ; Female ; Humans ; Knee ; Osteogenesis ; Rats, Nude ; Skin & tissue grafts ; Sports medicine ; Surgery ; Tendons - transplantation ; Tensile Strength ; Tibia - diagnostic imaging ; Tibia - physiology ; Tibia - surgery ; Time Factors ; Wound Healing - physiology ; X-Ray Microtomography</subject><ispartof>The American journal of sports medicine, 2017-05, Vol.45 (6), p.1359-1369</ispartof><rights>2017 The Author(s)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-aba0e666ba2fa5abcffc9da16e7bbd59875bc7ce6442e367161348e6ddfe910a3</citedby><cites>FETCH-LOGICAL-c431t-aba0e666ba2fa5abcffc9da16e7bbd59875bc7ce6442e367161348e6ddfe910a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0363546517689871$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0363546517689871$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21799,27903,27904,43600,43601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28282242$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inokuchi, Takao</creatorcontrib><creatorcontrib>Matsumoto, Tomoyuki</creatorcontrib><creatorcontrib>Takayama, Koji</creatorcontrib><creatorcontrib>Nakano, Naoki</creatorcontrib><creatorcontrib>Zhang, Shurong</creatorcontrib><creatorcontrib>Araki, Daisuke</creatorcontrib><creatorcontrib>Matsushita, Takehiko</creatorcontrib><creatorcontrib>Kuroda, Ryosuke</creatorcontrib><title>Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament–Derived Cells</title><title>The American journal of sports medicine</title><addtitle>Am J Sports Med</addtitle><description>Background:
Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time after injury on the healing process is unclear.
Hypothesis:
Cells obtained during the early phase after injury will exhibit a greater tendon-bone healing potential compared with chronic phase counterparts when applied to an immunodeficient rat model of ACL reconstruction.
Study Design:
Controlled laboratory study.
Methods:
Adult human ACL-ruptured tissue was harvested from patients undergoing arthroscopic primary ACL reconstruction and classified into 2 groups based on the time elapsed between injury and surgery: (1) early group (≤3 months from injury) and (2) chronic group (>3 months from injury). In addition, 76 ten-week-old female immunodeficient rats underwent ACL reconstruction, followed by intracapsular administration of one of the following: (1) ACL-derived cells from the early group (n = 5), (2) ACL-derived cells from the chronic group (n = 5), or (3) phosphate-buffered saline (PBS) only (n = 5). During the 8 weeks after surgery, histological (weeks 2, 4, 8), immunohistochemical (week 2), radiographic (weeks 0, 2, 4, 8), and biomechanical (week 8) analyses were performed to evaluate tendon-bone healing.
Results:
In the early group, the histological evaluation showed early healing, induction of endochondral ossification–like integration, and mature bone ingrowth. Micro–computed tomography showed that the tibial bone tunnels at week 4 and week 8 were significantly reduced in the early group compared with those in the chronic group and PBS group (P < .05). Moreover, biomechanical tensile strength was significantly greater in the early group than in the other groups (P < .05). An accelerated healing potential in the early group was further demonstrated by the enhancement of intrinsic angiogenesis/osteogenesis and human-derived vasculogenesis/osteogenesis.
Conclusion:
Compared with human ACL-derived cells obtained during the chronic phase, cells obtained during the early phase after injury have a greater tendon-bone healing potential when used in an immunodeficient rat model of ACL reconstruction.
Clinical Relevance:
During ACL reconstruction surgery, transplanting ACL remnant tissue in the early phase after injury could accelerate and enhance tendon-bone healing.</description><subject>Adult</subject><subject>Animals</subject><subject>Anterior Cruciate Ligament - cytology</subject><subject>Anterior Cruciate Ligament - surgery</subject><subject>Anterior Cruciate Ligament Reconstruction - methods</subject><subject>Biomechanics</subject><subject>Cell Differentiation</subject><subject>Cell Proliferation</subject><subject>Female</subject><subject>Humans</subject><subject>Knee</subject><subject>Osteogenesis</subject><subject>Rats, Nude</subject><subject>Skin & tissue grafts</subject><subject>Sports medicine</subject><subject>Surgery</subject><subject>Tendons - transplantation</subject><subject>Tensile Strength</subject><subject>Tibia - diagnostic imaging</subject><subject>Tibia - physiology</subject><subject>Tibia - surgery</subject><subject>Time Factors</subject><subject>Wound Healing - physiology</subject><subject>X-Ray Microtomography</subject><issn>0363-5465</issn><issn>1552-3365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1KxDAUhYMoOv7sXUnAjZtq0jZpu5TxZwYGFNR1SdObsUObaNIMzs538A19ElNHRQTJIpDz3XNv7kHokJJTSrPsjCQ8YSlnNON5kWd0A40oY3GUJJxtotEgR4O-g3adWxBCBnAb7cR5OHEaj9DLVKvWg5aAjcL9I-CpXni7inoT3Xk7B7sKLz3YpWix0Z_EBETb6Dm-NT3ovhkEhSe-ExqfD2hjLB5bLxvRA541c9EF7P317SJIS6jxGNrW7aMtJVoHB1_3Hnq4urwfT6LZzfV0fD6LZJrQPhKVIMA5r0SsBBOVVEoWtaAcsqqqWfg0q2QmgadpDAnPKKdJmgOvawUFJSLZQydr3ydrnj24vuwaJ8MEQoPxrqR5xhkhYR0BPf6DLoy3OkwXqCIPi8wLHiiypqQ1zllQ5ZNtOmFXJSXlkEr5N5VQcvRl7KsO6p-C7xgCEK0BJ-bwq-t_hh-y95Zn</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Inokuchi, Takao</creator><creator>Matsumoto, Tomoyuki</creator><creator>Takayama, Koji</creator><creator>Nakano, Naoki</creator><creator>Zhang, Shurong</creator><creator>Araki, Daisuke</creator><creator>Matsushita, Takehiko</creator><creator>Kuroda, Ryosuke</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TS</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>20170501</creationdate><title>Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament–Derived Cells</title><author>Inokuchi, Takao ; Matsumoto, Tomoyuki ; Takayama, Koji ; Nakano, Naoki ; Zhang, Shurong ; Araki, Daisuke ; Matsushita, Takehiko ; Kuroda, Ryosuke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-aba0e666ba2fa5abcffc9da16e7bbd59875bc7ce6442e367161348e6ddfe910a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Anterior Cruciate Ligament - cytology</topic><topic>Anterior Cruciate Ligament - surgery</topic><topic>Anterior Cruciate Ligament Reconstruction - methods</topic><topic>Biomechanics</topic><topic>Cell Differentiation</topic><topic>Cell Proliferation</topic><topic>Female</topic><topic>Humans</topic><topic>Knee</topic><topic>Osteogenesis</topic><topic>Rats, Nude</topic><topic>Skin & tissue grafts</topic><topic>Sports medicine</topic><topic>Surgery</topic><topic>Tendons - transplantation</topic><topic>Tensile Strength</topic><topic>Tibia - diagnostic imaging</topic><topic>Tibia - physiology</topic><topic>Tibia - surgery</topic><topic>Time Factors</topic><topic>Wound Healing - physiology</topic><topic>X-Ray Microtomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inokuchi, Takao</creatorcontrib><creatorcontrib>Matsumoto, Tomoyuki</creatorcontrib><creatorcontrib>Takayama, Koji</creatorcontrib><creatorcontrib>Nakano, Naoki</creatorcontrib><creatorcontrib>Zhang, Shurong</creatorcontrib><creatorcontrib>Araki, Daisuke</creatorcontrib><creatorcontrib>Matsushita, Takehiko</creatorcontrib><creatorcontrib>Kuroda, Ryosuke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of sports medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inokuchi, Takao</au><au>Matsumoto, Tomoyuki</au><au>Takayama, Koji</au><au>Nakano, Naoki</au><au>Zhang, Shurong</au><au>Araki, Daisuke</au><au>Matsushita, Takehiko</au><au>Kuroda, Ryosuke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament–Derived Cells</atitle><jtitle>The American journal of sports medicine</jtitle><addtitle>Am J Sports Med</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>45</volume><issue>6</issue><spage>1359</spage><epage>1369</epage><pages>1359-1369</pages><issn>0363-5465</issn><eissn>1552-3365</eissn><abstract>Background:
Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time after injury on the healing process is unclear.
Hypothesis:
Cells obtained during the early phase after injury will exhibit a greater tendon-bone healing potential compared with chronic phase counterparts when applied to an immunodeficient rat model of ACL reconstruction.
Study Design:
Controlled laboratory study.
Methods:
Adult human ACL-ruptured tissue was harvested from patients undergoing arthroscopic primary ACL reconstruction and classified into 2 groups based on the time elapsed between injury and surgery: (1) early group (≤3 months from injury) and (2) chronic group (>3 months from injury). In addition, 76 ten-week-old female immunodeficient rats underwent ACL reconstruction, followed by intracapsular administration of one of the following: (1) ACL-derived cells from the early group (n = 5), (2) ACL-derived cells from the chronic group (n = 5), or (3) phosphate-buffered saline (PBS) only (n = 5). During the 8 weeks after surgery, histological (weeks 2, 4, 8), immunohistochemical (week 2), radiographic (weeks 0, 2, 4, 8), and biomechanical (week 8) analyses were performed to evaluate tendon-bone healing.
Results:
In the early group, the histological evaluation showed early healing, induction of endochondral ossification–like integration, and mature bone ingrowth. Micro–computed tomography showed that the tibial bone tunnels at week 4 and week 8 were significantly reduced in the early group compared with those in the chronic group and PBS group (P < .05). Moreover, biomechanical tensile strength was significantly greater in the early group than in the other groups (P < .05). An accelerated healing potential in the early group was further demonstrated by the enhancement of intrinsic angiogenesis/osteogenesis and human-derived vasculogenesis/osteogenesis.
Conclusion:
Compared with human ACL-derived cells obtained during the chronic phase, cells obtained during the early phase after injury have a greater tendon-bone healing potential when used in an immunodeficient rat model of ACL reconstruction.
Clinical Relevance:
During ACL reconstruction surgery, transplanting ACL remnant tissue in the early phase after injury could accelerate and enhance tendon-bone healing.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>28282242</pmid><doi>10.1177/0363546517689871</doi><tpages>11</tpages></addata></record> |
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| identifier | ISSN: 0363-5465 |
| ispartof | The American journal of sports medicine, 2017-05, Vol.45 (6), p.1359-1369 |
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| language | eng |
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| source | MEDLINE; SAGE Publications; Alma/SFX Local Collection |
| subjects | Adult Animals Anterior Cruciate Ligament - cytology Anterior Cruciate Ligament - surgery Anterior Cruciate Ligament Reconstruction - methods Biomechanics Cell Differentiation Cell Proliferation Female Humans Knee Osteogenesis Rats, Nude Skin & tissue grafts Sports medicine Surgery Tendons - transplantation Tensile Strength Tibia - diagnostic imaging Tibia - physiology Tibia - surgery Time Factors Wound Healing - physiology X-Ray Microtomography |
| title | Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament–Derived Cells |
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